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The Evidence Behind Senescent Cells. And What Harms Can They Cause to Health?

senescent cells

Whether in denial or not, you’ll eventually have to deal with the inevitable aging symptoms of wrinkles, stiffening joints, and greying hair. Have you ever considered how all of these signs become visible?

Scientists have spent a lot of time trying to pinpoint what causes aging, and so far, they haven’t narrowed it down to a single biological element. Several interconnected mechanisms are believed to underlie the aging process known as hallmarks of aging. One of these mechanisms is senescent cell accumulation.

Senescent Cells are a major contributor to this aging process.

What is cell senescence, what causes it, and how can we eliminate senescent cells?

What is Senescence?

The word “senescence” denotesthe process of aging.” Throughout our lives, the cells of our bodies can receive external damage from the sun or chemicals in our environment. But the damage can also occur naturally due to natural processes like metabolism.

The concept of senescence was first discovered in 1960 by two scientists named Leonard Haylflick and Paul Moorhead. It was discovered that human cells in culture do not continue to divide indefinitely but instead enter a state of permanent slumber. Cell senescence refers to the process through which cells stop dividing (the word senescence comes from the Latin “Senex,” which means “old man” in Latin). Since then, many research teams have become interested in the hallmarks of senescence, the factors it leads to, and the effect of senescence on the other cells and the body as a whole.

How Does Senescence Work?

Our cells are generally very adept at repairing themselves and adapting to stress. However, our healing mechanisms weaken with age, and cell injury can have harmful effects. If cells are damaged, several outcomes are possible.

  • Ideally, the damage gets repaired, and the cell returns to its normal function.
  • But in some cases, the cell is irreparably damaged, so it dies in a controlled manner to stop damaging the surrounding cells and tissue. We call it programmed cell death or apoptosis.

Unfortunately, DNA alterations are brought on by cellular damage, resulting in excessive cell division without control and, ultimately, senescence.

This means senescent cells are able to bypass apoptosis, so even if they stop dividing, they don’t die off (programmed cell death). Thus, the term “zombie cells” is also used for them.

Moreover, cellular senescence has been linked to a wide range of age-associated diseases and disorders, such as cancer, diabetes, osteoporosis, cardiovascular disease, stroke, Alzheimer’s disease and related dementias, and osteoarthritis. It has also been associated with losing eyesight, movement, and cognitive function. Research is being conducted to determine whether senescent skin cells contribute to wrinkling and sagging and whether senescent cells are linked to the inflammatory cytokine storm that renders COVID-19 particularly lethal to the elderly.

Further, senescence is a defense mechanism that prevents cancer from forming, therefore, blocking cells from entering senescence when they should is a surefire way to ensure that an organism will get cancer.

Skin and adipose tissue are particularly rich in senescent cells.

 

https://www.nia.nih.gov/news/does-cellular-senescence-hold-secrets-healthier-aging#:~:text=They%20start%20accumulating%20when%20you,least%20some%20markers%20of%20senescence.

Why does it Cause Aging?

To make way for new, healthy cells, our systems are fine-tuned early to eliminate senescent ones. But as we age, our bodies manufacture more senescent cells and lose the capacity to sweep away the senescent cells they produce.

This stage of an individual’s life cycle is characterized by a slow decline after the peak of its productive years. That means human senescence would begin in your twenties, when you’re at the height of your physical prowess and last for the rest of your life.

Once people reach age 60, they begin to pile up exponentially. A percentage of tissues, up to 10% by the end of life, depending on how you’re aging, can show signs of senescence.

According to the results of a study conducted on primates in 2006, senescent cells do increase and can make up more than 15% of the total cell population in elderly people.

What Causes Senescence?

Senescence appears to be triggered when cells have undergone enough stress or damage to no longer recover. Radiation, chemicals, and viruses are just a few examples of outside agents that can put cells under stress and destroy them. Solar radiation or X-rays are two common examples. When you go to receive an X-ray, they give you a lead shield to put over your body. To keep your DNA and cells safe.

Overnutrition may also cause cellular senescence, according to a new 2021 study, suggesting a connection between diet and aging. Mice who are overweight appear to have an abundance of senescent cells in their fatty tissue. Moreover, the formation of reactive oxygen species (ROS) in the adipose tissue of obese people is elevated.

But not every senescent cell is harmful. The senescent secretome refers to the chemicals and substances expressed by senescent cells and has crucial roles throughout the lifespan, from embryonic development through childbirth to wound healing. Such processes are aided by the development of senescent cells, which serve as a transient patch and eventually die off, reducing scar tissue.

How to Slow Down Cellular Senescence?

Now the challenge is, how can we eliminate senescent cells and stop them from growing in the first place? How may we delay the accumulation of senescent cells as we age?

Research and clinical interest have been sparked by animal research findings, leading to the creation of specific medications that can eradicate senescent cells that contribute to age-related diseases. Therapeutically relevant approaches against cell senescence can be characterized as one of the following:

  • Interventions other than medicines that inhibit the formation of senescent cells, such as exercise.
  • Pharmacological treatments to lessen the body’s accumulation of senescent cells

Scientists have discovered, and there is clear evidence, that destroying senescent cells and limiting the growth of senescent cells is not only doable, but it’s an effective approach to delaying aging and age-related disorders.

To reverse the effects of cellular senescence associated with aging, it is possible to eradicate senescent cells with drugs known as senolytics. They work by eliminating senescent cells, which contribute to many diseases, senolytic drugs are seen as a promising tool for slowing the aging process.

senolytics and cellular senescence

https://www.frontiersin.org/articles/10.3389/fcell.2019.00367/full

Several age-related diseases in mice are delayed, prevented, or alleviated by their use.

In Animals:

Senolytic drugs have been reported to improve cardiac function in mice, increase insulin sensitivity, reduce adipose tissue inflammation, and alleviate several age-related diseases in which the accumulation of senescent cells plays a role in their pathogenesis, such as Alzheimer’s disease, chronic lung diseases, osteoporosis, and intervertebral disc disease.

Animal research demonstrated that the systematic elimination of senescence cells in mice delayed the onset of cataracts and improved age-related muscle atrophy and function. (1)

It was observed in 2021 that the age-related degeneration of the mice’s intervertebral discs was slowed by chronic treatment of the senolytic medicines Dasatinib, a tyrosine kinase inhibitor, and Quercetin, a naturally occurring flavonoid. Mice given these drugs for almost two years had less disc degeneration and senescence-related biomarkers.

In Humans: In early 2019, scientists proved that senolytics could effectively eliminate senescent cells without harming healthy cells. This research involved 14 people who were diagnosed with idiopathic pulmonary fibrosis. The study’s primary objective was to assess the treatment’s safety. And the results suggested that three weeks of oral dosing once a week improved performance on a variety of physical measures, including the 6-minute walk distance and the ability to get out of a chair without assistance.

A similar combination was reported to lessen senescent cell accumulation in diabetic renal disease patients’ fatty tissue in a preliminary investigation.

Dasatinib, a medicine used to treat leukaemia, and quercetin, a vitamin, have just been shown in a revolutionary human trial to drastically lower the number of senescent cells in the bodies of aged adults in just three days.

More and more research is focusing on senolytic compounds that can either control senescence or destroy senescent cells to increase lifespan and Healthspan.

Non-Pharmacological Treatment:

There is no imminent need for therapy to destroy senescent cells in the body. The solution may lie in physical activity too.

It is proven that it’s within your power to slow down the aging process by activating your body’s natural healing potential through physical activity and exercise.

Last year in 2021, a study showed for the first time in humans that exercise can considerably lower signs detected in the circulation of a load of senescent cells. According to the study’s authors, improved muscle strength, physical function, and self-reported health were among the benefits of a 12-week aerobics, resistance, and balance training program for older adults.

Another method that can be used is starting a low-calorie diet to lower the number of senescent cells in proliferating tissues.

What’s The best Senolytic?

Many different types of naturally occurring chemicals have the potential to be senolytic.

  • Quercetin is a polyphenolic flavonoid molecule with antioxidant capabilities that has been shown to reduce the risk of developing several different diseases, such as osteoporosis, some forms of cancer, tumors, and lung and cardiovascular diseases. The scientific research into quercetin’s senolytic properties has been building up for years. (1) (2) (3) (4)

As far as natural senolytics go, however, fisetin appears to be the most effective.

  • Many animal studies have ruled out the usage of flavonoids as senolytics, as out of the ten flavonoids evaluated, Fisetin had the greatest senolytic activity. Over 70% of senescent cells were destroyed, without harming normal, healthy human cells, according to a cell study published in the journal Aging. In another study, elderly mice given fisetin lived approximately 10%. According to this concept, a person 75 years old might live another 7.5 years.
  • Combining tocotrienols with quercetin, a flavonol in many fruits and vegetables has demonstrated positive effects in studies. It has been proven to cause cell death and senescence in many different cancers.

 

In a healthy organism, senescent cells are essential for cellular homeostasis and the prevention of malignant transformation by suppressing the proliferation of malignant tumors. Natural killer cells generally eliminate them, allowing the body to reap the benefits of cellular senescence.  Yet, senescent cells accumulate with age because they are created faster, while natural killer cells are produced at a lower rate. However, an abnormally high number of senescent cells in the body might trigger age-related diseases, including cancer.

Senolytics are the drugs that are shown to be effective and safe in humans, they could be “transformative” in eliminating or delaying chronic illnesses collectively rather than individually. Research is ongoing in this regard to prove their efficacy and accuracy for different types of disorders as well as for extending lifespan.

 

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